Liver transplantation is the treatment of choice for selected patients with hepatocellular carcinoma (HCC) on a background of chronic liver disease. Liver resection or locoregional ablative therapies may be indicated for patients with preserved synthetic function without significant portal hypertension. Milan criteria were introduced to select suitable patients for liver transplant with low risk of tumor recurrence and 5-year survival in excess of 70%. Currently the incidence of HCC is climbing rapidly and in a current climate of organ shortage has led to the re-evaluation of locoregional therapies and resectional surgery to manage the case load. The introduction of biological therapies has had a new dimension to care, adding to the complexities of multidisciplinary team working in the management of HCC. The aim of this paper is to give a brief overview of present day management strategies and decision making. 1. Introduction Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Ninety percent of primary liver cancers are HCC, the majority of which develop on the background of cirrhosis. Over the past decade, medical management of the patient with chronic liver disease has improved. In parallel, the prevalence of hepatitis B (HBV), hepatitis C virus (HCV), alcohol related liver disease, and NASH has increased and combined with an ageing population has led to a surge in the number of cases worldwide [1–3]. As a consequence, HCC is an important complication of cirrhosis and a leading indication for liver transplantation (LT), accounting for approximately a third of patients on transplant waiting lists [4]. The introduction of surveillance using alphafetoprotein and ultrasound has led to the earlier recognition of HCC and increases the therapeutic options available [5]. In the absence of treatment the overall 5-year survival is <10% [6]. These include LT, resection, locoregional, and systemic therapies. For a solitary HCC with preserved liver function and low hepatic vein pressure gradient, liver resection still remains the first choice. Historically, survival rates were 35–62% at 3 years and 17–50% at 5 years for patients with cirrhosis undergoing resection for HCC [6, 7]. However, tumor recurrence rates were high, up to 70%, and progression to liver failure was common [6, 8–10]. LT is an attractive treatment option as it treats both the cancer and underlying liver disease. In the 1980s, patients presenting with large HCC were considered good candidates for LT as they were in better condition than patients with chronic liver disease
References
[1]
H. B. El-Serag and A. C. Mason, “Rising incidence of hepatocellular carcinoma in the United States,” The New England Journal of Medicine, vol. 340, no. 10, pp. 745–750, 1999.
[2]
F. X. Bosch, J. Ribes, M. Díaz, and R. Cléries, “Primary liver cancer: worldwide incidence and trends,” Gastroenterology, vol. 127, supplement 1, pp. S5–S16, 2004.
[3]
H. B. El-Serag and K. L. Rudolph, “Hepatocellular carcinoma: epidemiology and molecular carcinogenesis,” Gastroenterology, vol. 132, no. 7, pp. 2557–2576, 2007.
[4]
D. Samuel, M. Colombo, H. El-Serag, R. Sobesky, and N. Heaton, “Toward optimizing the indications for orthotopic liver transplantation in hepatocellular carcinoma,” Liver Transplantation, vol. 17, supplement 2, pp. S6–S13, 2011.
[5]
V. Santi, F. Trevisani, A. Gramenzi et al., “Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival,” Journal of Hepatology, vol. 53, no. 2, pp. 291–297, 2010.
[6]
J. M. Llovet, J. Fuster, and J. Bruix, “Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation,” Hepatology, vol. 30, no. 6, pp. 1434–1440, 1999.
[7]
D. Franco, L. Capussotti, C. Smadja et al., “Resection of hepatocellular carcinomas. Reults in 72 European patients with cirrhosis,” Gastroenterology, vol. 98, no. 3, pp. 733–738, 1990.
[8]
S. Okada, K. Shimada, J. Yamamoto et al., “Predictive factors for postoperative recurrence of hepatocellular carcinoma,” Gastroenterology, vol. 106, no. 6, pp. 1618–1624, 1994.
[9]
M. Minagawa, M. Makuuchi, T. Takayama, and N. Kokudo, “Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma,” Annals of Surgery, vol. 238, no. 5, pp. 703–710, 2003.
[10]
R. T. P. Poon, S. T. Fan, C. M. Lo, C. L. Liu, and J. Wong, “Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors,” Annals of Surgery, vol. 229, no. 2, pp. 216–222, 1999.
[11]
J. G. O'Grady, R. J. Polson, K. Rolles, R. Y. Calne, and R. Williams, “Liver transplantation for malignant disease,” Annals of Surgery, vol. 207, no. 4, pp. 373–379, 1988.
[12]
B. Ringe, R. Pichlmayr, C. Wittekind, and G. Tusch, “Surgical treatment of hepatocellular carcinoma: experience with liver resection and transplantation in 198 patients,” World Journal of Surgery, vol. 15, no. 2, pp. 270–285, 1991.
[13]
P. Moreno, E. Jaurrieta, J. Figueras et al., “Orthotopic liver transplantation: treatment of choice in cirrhotic patients with hepatocellular carcinoma?” Transplantation Proceedings, vol. 27, no. 4, pp. 2296–2298, 1995.
[14]
V. Mazzaferro, E. Regalia, R. Doci et al., “Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis,” The New England Journal of Medicine, vol. 334, no. 11, pp. 693–699, 1996.
[15]
K. M. Olthoff, A. Forner, S. Hübscher, and J. Fung, “What is the best staging system for hepatocellular carcinoma in the setting of liver transplantation?” Liver Transplantation, vol. 17, supplement 2, pp. S26–S33, 2011.
[16]
F. Y. Yao, L. Ferrell, N. M. Bass et al., “Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival,” Hepatology, vol. 33, no. 6, pp. 1394–1403, 2001.
[17]
V. Mazzaferro, J. M. Llovet, R. Miceli et al., “Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis,” The Lancet Oncology, vol. 10, no. 1, pp. 35–43, 2009.
[18]
S. Roayaie, J. S. Frischer, S. H. Emre et al., “Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters,” Annals of Surgery, vol. 235, no. 4, pp. 533–539, 2002.
[19]
N. M. Kneteman, J. Oberholzer, M. Al Saghier et al., “Sirolimus-based immunosuppression for liver transplantation in the presence of extended criteria for hepatocellular carcinoma,” Liver Transplantation, vol. 10, no. 10, pp. 1301–1311, 2004.
[20]
P. E. Majno, F. P. Sarasin, G. Mentha, and A. Hadengue, “Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: an outcome-oriented decision analysis,” Hepatology, vol. 31, no. 4, pp. 899–906, 2000.
[21]
D. Fuks, S. Dokmak, V. Paradis, M. Diouf, F. Durand, and J. Belghiti, “Benefit of initial resection of hepatocellular carcinoma followed by transplantation in case of recurrence: an intention-to-treat analysis,” Hepatology, vol. 55, no. 1, pp. 132–140, 2012.
[22]
R. Adam, D. Azoulay, D. Castaing et al., “Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy?” Annals of Surgery, vol. 238, no. 4, pp. 508–519, 2003.
[23]
P. E. Majno, R. Adam, H. Bismuth et al., “Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis,” Annals of Surgery, vol. 226, no. 6, pp. 688–703, 1997.
[24]
I. W. Graziadei, H. Sandmueller, P. Waldenberger et al., “Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome,” Liver Transplantation, vol. 9, no. 6, pp. 557–563, 2003.
[25]
F. Y. Yao, S. Breitenstein, C. E. Broelsch, et al., “Does a patient qualify for liver transplantation after the down-staging of hepatocellular carcinoma?” Liver Transplantation, vol. 17, supplement 2, pp. S109–S116, 2011.
[26]
O. Barakat, R. P. Wood, C. F. Ozaki et al., “Morphological features of advanced hepatocellular carcinoma as a predictor of downstaging and liver transplantation: an intention-to-treat analysis,” Liver Transplantation, vol. 16, no. 3, pp. 289–299, 2010.
[27]
F. Y. Yao, R. K. Kerlan Jr., R. Hirose et al., “Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis,” Hepatology, vol. 48, no. 3, pp. 819–827, 2008.
[28]
W. Y. Lau and E. C. H. Lai, “Salvage surgery following downstaging of unresectable hepatocellular carcinoma—a strategy to increase resectability,” Annals of Surgical Oncology, vol. 14, no. 12, pp. 3301–3309, 2007.
[29]
M. Ravaioli, G. L. Grazi, F. Piscaglia et al., “Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria,” American Journal of Transplantation, vol. 8, no. 12, pp. 2547–2557, 2008.
[30]
R. J. Lewandowski, L. M. Kulik, A. Riaz et al., “A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization,” American Journal of Transplantation, vol. 9, no. 8, pp. 1920–1928, 2009.
[31]
L. Kulik and M. Abecassis, “Living donor liver transplantation for hepatocellular carcinoma,” Gastroenterology, vol. 127, supplement 1, pp. S277–S282, 2004.
[32]
S. Di Sandro, A. O. Slim, A. Giacomoni et al., “Living donor liver transplantation for hepatocellular carcinoma: long-term results compared with deceased donor liver transplantation,” Transplantation Proceedings, vol. 41, no. 4, pp. 1283–1285, 2009.
[33]
K. Vakili, J. J. Pomposelli, Y. L. Cheah et al., “Living donor liver transplantation for hepatocellular carcinoma: Increased recurrence but improved survival,” Liver Transplantation, vol. 15, no. 12, pp. 1861–1866, 2009.
[34]
R. S. Mangus, J. A. Fridell, R. M. Vianna, A. B. Cooper, D. T. Jones, and A. J. Tector, “Use of the piggyback hepatectomy technique in liver transplant recipients with hepatocellular carcinoma,” Transplantation, vol. 85, no. 10, pp. 1496–1499, 2008.
[35]
P. A. Clavien, M. Lesurtel, P. M. Bossuyt et al., “Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report,” The Lancet Oncology, vol. 13, pp. e11–e22, 2012.
[36]
P. Bhangui, E. Vibert, P. Majno et al., “Intention-to-treat analysis of liver transplantation for hepatocellular carcinoma: living versus deceased donor transplantation,” Hepatology, vol. 53, no. 5, pp. 1570–1579, 2011.
[37]
J. Chen, K. Huang, J. Wu et al., “Survival after anatomic resection versus nonanatomic resection for hepatocellular carcinoma: a meta-analysis,” Digestive Diseases and Sciences, vol. 56, no. 6, pp. 1626–1633, 2011.
[38]
R. T. P. Poon, S. T. Fan, C. M. Lo et al., “Extended hepatic resection for hepatocellular carcinoma in patients with cirrhosis: is it justified?” Annals of Surgery, vol. 236, no. 5, pp. 602–611, 2002.
[39]
H. Imamura, Y. Matsuyama, E. Tanaka et al., “Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy,” Journal of Hepatology, vol. 38, no. 2, pp. 200–207, 2003.
[40]
M. Samuel, P. K. Chow, E. Chan Shih-Yen, D. Machin, and K. C. Soo, “Neoadjuvant and adjuvant therapy for surgical resection of hepatocellular carcinoma,” Cochrane Database of Systematic Reviews, no. 1, article CD001199, 2009.
[41]
A. Abulkhir, P. Limongelli, A. J. Healey et al., “Preoperative portal vein embolization for major liver resection: a meta-analysis,” Annals of Surgery, vol. 247, no. 1, pp. 49–57, 2008.
[42]
K. P. Croome and M. H. Yamashita, “Laparoscopic vs open hepatic resection for benign and malignant tumors: an updated meta-analysis,” Archives of Surgery, vol. 145, no. 11, pp. 1109–1118, 2010.
[43]
T. Livraghi, F. Meloni, M. Di Stasi et al., “Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice?” Hepatology, vol. 47, no. 1, pp. 82–89, 2008.
[44]
Y. K. Cho, J. K. Kim, M. Y. Kim, H. Rhim, and J. K. Han, “Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies,” Hepatology, vol. 49, no. 2, pp. 453–459, 2009.
[45]
R. Lencioni, “Loco-regional treatment of hepatocellular carcinoma,” Hepatology, vol. 52, no. 2, pp. 762–773, 2010.
[46]
S. Tanaka, M. Shimada, K. Shirabe et al., “Surgical radiofrequency ablation for treatment of hepatocellular carcinoma: an endoscopic or open approach,” Hepato-Gastroenterology, vol. 56, no. 93, pp. 1169–1173, 2009.
[47]
F. Di Benedetto, G. Tarantino, R. Montalti et al., “Laparoscopic radiofrequency ablation in the caudate lobe for hepatocellular carcinoma before liver transplantation,” Journal of Laparoendoscopic & Advanced Surgical Techniques, vol. 22, no. 4, pp. 400–402, 2012.
[48]
Y. K. Cho, J. K. Kim, W. T. Kim, and J. W. Chung, “Hepatic resection versus radiofrequency ablation for very early stage hepatocellular carcinoma: a markov model analysis,” Hepatology, vol. 51, no. 4, pp. 1284–1290, 2010.
[49]
M. S. Chen, J. Q. Li, Y. Zheng et al., “A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma,” Annals of Surgery, vol. 243, no. 3, pp. 321–328, 2006.
[50]
C. Cammà, V. Di Marco, A. Orlando et al., “Treatment of hepatocellular carcinoma in compensated cirrhosis with radio-frequency thermal ablation (RFTA): a prospective study,” Journal of Hepatology, vol. 42, no. 4, pp. 535–540, 2005.
[51]
R. Tateishi, S. Shiina, T. Teratani et al., “Percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1000 cases,” Cancer, vol. 103, no. 6, pp. 1201–1209, 2005.
[52]
J. Huang, L. Yan, Z. Cheng et al., “A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria,” Annals of Surgery, vol. 252, no. 6, pp. 903–912, 2010.
[53]
M. Morimoto, K. Numata, M. Kondou, A. Nozaki, S. Morita, and K. Tanaka, “Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization,” Cancer, vol. 116, no. 23, pp. 5452–5460, 2010.
[54]
A. Veltri, P. Moretto, A. Doriguzzi, E. Pagano, G. Carrara, and G. Gandini, “Radiofrequency thermal ablation (RFA) after transarterial chemoembolization (TACE) as a combined therapy for unresectable non-early hepatocellular carcinoma (HCC),” European Radiology, vol. 16, no. 3, pp. 661–669, 2006.
[55]
A. Forner, C. Ayuso, M. Varela et al., “Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: are response evaluation criteria in solid tumors reliable?” Cancer, vol. 115, no. 3, pp. 616–623, 2009.
[56]
J. M. Llovet and J. Bruix, “Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival,” Hepatology, vol. 37, no. 2, pp. 429–442, 2003.
[57]
J. L. Raoul, B. Sangro, A. Forner et al., “Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization,” Cancer Treatment Reviews, vol. 37, no. 3, pp. 212–220, 2011.
[58]
M. Varela, M. I. Real, M. Burrel et al., “Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics,” Journal of Hepatology, vol. 46, no. 3, pp. 474–481, 2007.
[59]
J. Lammer, K. Malagari, T. Vogl et al., “Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION v study,” CardioVascular and Interventional Radiology, vol. 33, no. 1, pp. 41–52, 2010.
[60]
G. Cabibbo, M. Enea, M. Attanasio, J. Bruix, A. Craxì, and C. Cammá, “A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma,” Hepatology, vol. 51, no. 4, pp. 1274–1283, 2010.
[61]
J. Luo, R. P. Guo, E. C. H. Lai et al., “Transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a prospective comparative study,” Annals of Surgical Oncology, vol. 18, no. 2, pp. 413–420, 2011.
[62]
L. M. Kulik, B. I. Carr, M. F. Mulcahy et al., “Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis,” Hepatology, vol. 47, no. 1, pp. 71–81, 2008.
[63]
L. M. Kulik, B. Atassi, L. van Holsbeeck et al., “Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation,” Journal of Surgical Oncology, vol. 94, no. 7, pp. 572–586, 2006.
[64]
B. Sangro, M. I？arrairaegui, and J. I. Bilbao, “Radioembolization for hepatocellular carcinoma,” Journal of Hepatology, vol. 56, no. 2, pp. 464–473, 2012.
[65]
R. Salem, R. J. Lewandowski, L. Kulik et al., “Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma,” Gastroenterology, vol. 140, no. 2, pp. 497–507, 2011.
[66]
J. K. Kang, M. S. Kim, C. K. Cho, et al., “Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization,” Cancer, vol. 118, no. 21, pp. 5424–5431, 2012.
[67]
A. Takeda, M. Takahashi, E. Kunieda et al., “Hypofractionated stereotactic radiotherapy with and without transarterial chemoembolization for small hepatocellular carcinoma not eligible for other ablation therapies: preliminary results for efficacy and toxicity,” Hepatology Research, vol. 38, no. 1, pp. 60–69, 2008.
[68]
R. V. Tse, M. Hawkins, G. Lockwood et al., “Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma,” Journal of Clinical Oncology, vol. 26, no. 4, pp. 657–664, 2008.
[69]
J. H. Kwon, S. H. Bae, J. Y. Kim et al., “Long-term effect of stereotactic body radiation therapy for primary hepatocellular carcinoma ineligible for local ablation therapy or surgical resection. Stereotactic radiotherapy for liver cancer,” BMC Cancer, vol. 10, article 475, 2010.
[70]
J. F. Perz, G. L. Armstrong, L. A. Farrington, Y. J. F. Hutin, and B. P. Bell, “The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide,” Journal of Hepatology, vol. 45, no. 4, pp. 529–538, 2006.
[71]
H. I. Yang, S. N. Lu, Y. F. Liaw, et al., “Hepatitis B e antigen and the risk of hepatocellular carcinoma,” The New England Journal of Medicine, vol. 347, pp. 168–174, 2002.
[72]
H. L. Y. Chan, C. H. Tse, F. Mo et al., “High viral load and hepatitis B virus subgenotype Ce are associated with increased risk of hepatocellular carcinoma,” Journal of Clinical Oncology, vol. 26, no. 2, pp. 177–182, 2008.
[73]
Y. F. Liaw, J. J. Sung, W. C. Chow, et al., “Lamivudine for patients with chronic hepatitis B and advanced liver disease,” The New England Journal of Medicine, vol. 351, pp. 1521–1531, 2004.
[74]
J. S. W. Wong, G. L. H. Wong, K. K. F. Tsoi et al., “Meta-analysis: the efficacy of anti-viral therapy in prevention of recurrence after curative treatment of chronic hepatitis B-related hepatocellular carcinoma,” Alimentary Pharmacology and Therapeutics, vol. 33, no. 10, pp. 1104–1112, 2011.
[75]
S. Raimondi, S. Bruno, M. U. Mondelli, and P. Maisonneuve, “Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis,” Journal of Hepatology, vol. 50, no. 6, pp. 1142–1154, 2009.
[76]
L. T. Chen, M. F. Chen, L. A. Li, et al., “Long-term results of a randomized, observation-controlled, phase III trial of adjuvant interferon Alfa-2b in hepatocellular carcinoma after curative resection,” Annals of Surgery, vol. 255, no. 1, pp. 8–17, 2012.
[77]
F. Sahin, R. Kannangai, O. Adegbola, J. Wang, G. Su, and M. Torbenson, “mTOR and P70 S6 kinase expression in primary liver neoplasms,” Clinical Cancer Research, vol. 10, no. 24, pp. 8421–8425, 2004.
[78]
A. Valdivieso, J. Bustamante, M. Gastaca et al., “Management of hepatocellular carcinoma recurrence after liver transplantation,” Transplantation Proceedings, vol. 42, no. 2, pp. 660–662, 2010.
[79]
J. M. Alamo, L. Barrera, M. D. Casado et al., “Efficacy, tolerance, and safety of mammalian target of rapamycin inhibitors as rescue immunosuppressants in liver transplantation,” Transplantation Proceedings, vol. 41, no. 6, pp. 2181–2183, 2009.
[80]
M. Vivarelli, A. Dazzi, M. Zanello et al., “Effect of different immunosuppressive schedules on recurrence-free survival after liver transplantation for hepatocellular carcinoma,” Transplantation, vol. 89, no. 2, pp. 227–231, 2010.
[81]
G. S？derdahl, L. B？ckman, H. Isoniemi et al., “A prospective, randomized, multi-centre trial of systemic adjuvant chemotherapy versus no additional treatment in liver transplantation for hepatocellular carcinoma,” Transplant International, vol. 19, no. 4, pp. 288–294, 2006.
[82]
H. Pokorny, M. Gnant, S. Rasoul-Rockenschaub et al., “Does additional doxorubicin chemotherapy improve outcome in patients with hepatocellular carcinoma treated by liver transplantation?” American Journal of Transplantation, vol. 5, no. 4, pp. 788–794, 2005.
[83]
J. M. Llovet, S. Ricci, V. Mazzaferro et al., “Sorafenib in advanced hepatocellular carcinoma,” The New England Journal of Medicine, vol. 359, no. 4, pp. 378–390, 2008.
[84]
European Association for the Study of the Liver and European Organisation for Research and Treatment of Cancer, “EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma,” Journal of Hepatology, vol. 56, no. 4, pp. 908–943, 2012.
[85]
R. Kim, G. El-Gazzaz, A. Tan et al., “Safety and feasibility of using sorafenib in recurrent hepatocellular carcinoma after orthotopic liver transplantation,” Oncology, vol. 79, no. 1-2, pp. 62–66, 2010.
[86]
M. Yeganeh, R. S. Finn, and S. Saab, “Apparent remission of a solitary metastatic pulmonary lesion in a liver transplant recipient treated with sorafenib,” American Journal of Transplantation, vol. 9, no. 12, pp. 2851–2854, 2009.
[87]
A. Villanueva and J. M. Llovet, “Targeted therapies for hepatocellular carcinoma,” Gastroenterology, vol. 140, no. 5, pp. 1410–1426, 2011.
